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Erlotinib and Chemotherapy for 2nd Line Treatment (Tx) of Metastatic Colorectal Cancer (mCRC)

Primary Purpose

Metastatic Colorectal Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Erlotinib
Fluorouracil
Leucovorin
Oxaliplatin
Irinotecan
Sponsored by
OHSU Knight Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Colon, Cancer, Metastatic, Colorectal

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must fulfill all of the following criteria to be eligible for study entry:

  • Age 18-80
  • Able to provide informed consent
  • Biopsy proven unresectable metastatic adenocarcinoma of the colon or rectum
  • Documented progression on prior first-line oxaliplatin-based or irinotecan-based regimen for metastatic colorectal cancer
  • Radiographically measurable disease with at least one bidimensionally measurable lesion of > 1 cm
  • Prior first-line regimen must have been completed at least 4 weeks prior to study treatment
  • Use of biologic agents with first-line chemotherapy permitted
  • Previous adjuvant regimens must have been greater than 6 months before inclusion
  • Adequate organ function including bone marrow, liver and renal function as defined by the following values: absolute neutrophil count > 1500/microliter; Hgb > 9 g/dL; platelets > 90,000/microliter; International Normalized Ratio < 1.8 (unless in therapeutic range if taking warfarin or other warfarin-derivative anticoagulants and are being monitored regularly for changes in prothrombin time or International Normalized Ratio); bilirubin < 2 times the Upper Limit of Normal; alkaline phosphatase < 3 times the Upper Limit of Normal; aspartate aminotransferase/alanine aminotransferase < 5 times the Upper Limit of Normal; serum creatinine < 1.5 times the Upper Limit of Normal
  • Eastern Cooperative Oncology Group status < 2

Exclusion Criteria:

Patients meeting any of the following criteria are ineligible for study entry:

  • Prior second-line chemotherapy regimens for colorectal cancer
  • Prior treatment with erlotinib or gefitinib
  • Central Nervous System metastasis
  • Second malignancies less than 5 years prior to enrollment. Completely resected basal or squamous cell carcinoma of the skin is allowed.
  • Untreated/unresolved bowel obstruction
  • Inability to take oral mediations
  • HIV positive
  • Pregnancy
  • Other uncontrolled medical illnesses
  • Current diarrhea > grade 2
  • Symptomatic angina or uncontrolled congestive heart failure

Sites / Locations

  • Oregon Health & Science University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

FOLFOX with Erlotinib

FOLFIRI with Erlotinib

Arm Description

Subjects received FOLFOX (Leucovorin, Fluorouracil, and Oxaliplatin) and Erlotinib. Treatment consisted of a 28 day cycle. Subjects received FOLFOX on days 1, 2, and 3, and 15-16, followed by Erlotinib on days 3-8, and 17-22.

Subjects received FOLFIRI (Leucovorin, Fluorouracil, and Irinotecan) and Erlotinib. Treatment consisted of a 28 day cycle. Subjects received FOLFIRI on days 1, 2, and 3, and 15-16, followed by Erlotinib on days 3-8, and 17-22.

Outcomes

Primary Outcome Measures

Response Rates of Radiographically Measurable Disease
The primary outcome measure will be the response rates of radiographically measurable disease. Response rate of disease will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.

Secondary Outcome Measures

Second-line Progression Free Survival
Time to disease progression from start of second-line experimental regimen. Disease progression will be measured per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Time to Second Progression (From Start of First-Line Regimen)
Number of days from the initiation of first line treatment to first documented progression. Progression will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. Progression free survival (time to progression or death, whichever occurs first) is the same as time to progression as all of the patients in this trial progressed.

Full Information

First Posted
March 24, 2008
Last Updated
September 24, 2014
Sponsor
OHSU Knight Cancer Institute
Collaborators
Genentech, Inc., OSI Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00642746
Brief Title
Erlotinib and Chemotherapy for 2nd Line Treatment (Tx) of Metastatic Colorectal Cancer (mCRC)
Official Title
Phase II Study of Erlotinib (Tarceva) Alternating With Chemotherapy for Second-line Treatment of Metastatic Colorectal Cancer With Molecular Correlates for p53 Pathway
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Terminated
Why Stopped
Terminated due to poor enrollment and grade 3 toxicities noted during an interim analysis.
Study Start Date
March 2008 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OHSU Knight Cancer Institute
Collaborators
Genentech, Inc., OSI Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to see if alternating chemotherapy with erlotinib increases tumor shrinkage in people with metastatic colorectal cancer. The investigator will also be studying the side effects (good and bad) of alternating chemotherapy with erlotinib on metastatic colorectal cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Colon, Cancer, Metastatic, Colorectal

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FOLFOX with Erlotinib
Arm Type
Experimental
Arm Description
Subjects received FOLFOX (Leucovorin, Fluorouracil, and Oxaliplatin) and Erlotinib. Treatment consisted of a 28 day cycle. Subjects received FOLFOX on days 1, 2, and 3, and 15-16, followed by Erlotinib on days 3-8, and 17-22.
Arm Title
FOLFIRI with Erlotinib
Arm Type
Experimental
Arm Description
Subjects received FOLFIRI (Leucovorin, Fluorouracil, and Irinotecan) and Erlotinib. Treatment consisted of a 28 day cycle. Subjects received FOLFIRI on days 1, 2, and 3, and 15-16, followed by Erlotinib on days 3-8, and 17-22.
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Other Intervention Name(s)
Tarceva
Intervention Description
Erlotinib oral tablets are conventional, immediate-release tablets containing erlotinib as the hydrochloride salt. In addition to the active ingredient, erlotinib contains lactose (hydrous), microcrystalline cellulose, sodium starch glycolate, sodium lauryl sulfate, and magnesium stearate. Tablets containing 25 mg, 100 mg, and 150 mg of erlotinib are available. Each bottle will contain 30 tablets, a quantity sufficient for 4 consecutive weeks of dosing, with overage.
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Intervention Description
Antimetabolite used as a chemotherapy. Administered intravenously as a bolus injection at 400mg/m2 on Day 1 followed by 2400 mg/m2 continuously over 46 hours.
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Intervention Description
Chemotherapy agent given as a supplement to Fluorouracil. Given intravenously 400mg/m2 in combination with Fluorouracil dosing.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Platinum-based antineoplastic chemotherapy agent given intravenously at 85 mg/m2.
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Chemotherapy agent given intravenously at 180 mg/m2.
Primary Outcome Measure Information:
Title
Response Rates of Radiographically Measurable Disease
Description
The primary outcome measure will be the response rates of radiographically measurable disease. Response rate of disease will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Time Frame
Disease response assessed after every 2 Treatment Cycles, or around 8 weeks.
Secondary Outcome Measure Information:
Title
Second-line Progression Free Survival
Description
Time to disease progression from start of second-line experimental regimen. Disease progression will be measured per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Time Frame
Upon completion of follow-up, for an average of 99 days following the initiation of study treatment.
Title
Time to Second Progression (From Start of First-Line Regimen)
Description
Number of days from the initiation of first line treatment to first documented progression. Progression will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >= 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. Progression free survival (time to progression or death, whichever occurs first) is the same as time to progression as all of the patients in this trial progressed.
Time Frame
Documented by Follow-up CT scans following first line treatment, average of 225 days.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must fulfill all of the following criteria to be eligible for study entry: Age 18-80 Able to provide informed consent Biopsy proven unresectable metastatic adenocarcinoma of the colon or rectum Documented progression on prior first-line oxaliplatin-based or irinotecan-based regimen for metastatic colorectal cancer Radiographically measurable disease with at least one bidimensionally measurable lesion of > 1 cm Prior first-line regimen must have been completed at least 4 weeks prior to study treatment Use of biologic agents with first-line chemotherapy permitted Previous adjuvant regimens must have been greater than 6 months before inclusion Adequate organ function including bone marrow, liver and renal function as defined by the following values: absolute neutrophil count > 1500/microliter; Hgb > 9 g/dL; platelets > 90,000/microliter; International Normalized Ratio < 1.8 (unless in therapeutic range if taking warfarin or other warfarin-derivative anticoagulants and are being monitored regularly for changes in prothrombin time or International Normalized Ratio); bilirubin < 2 times the Upper Limit of Normal; alkaline phosphatase < 3 times the Upper Limit of Normal; aspartate aminotransferase/alanine aminotransferase < 5 times the Upper Limit of Normal; serum creatinine < 1.5 times the Upper Limit of Normal Eastern Cooperative Oncology Group status < 2 Exclusion Criteria: Patients meeting any of the following criteria are ineligible for study entry: Prior second-line chemotherapy regimens for colorectal cancer Prior treatment with erlotinib or gefitinib Central Nervous System metastasis Second malignancies less than 5 years prior to enrollment. Completely resected basal or squamous cell carcinoma of the skin is allowed. Untreated/unresolved bowel obstruction Inability to take oral mediations HIV positive Pregnancy Other uncontrolled medical illnesses Current diarrhea > grade 2 Symptomatic angina or uncontrolled congestive heart failure
Facility Information:
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States

12. IPD Sharing Statement

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Erlotinib and Chemotherapy for 2nd Line Treatment (Tx) of Metastatic Colorectal Cancer (mCRC)

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